System and method to managing stimulation of select a-beta fiber components

ABSTRACT

A computer implemented method and system is provided for managing neural stimulation therapy. The method comprises under control of one or more processors configured with program instructions. The method delivers a series of candidate stimulation waveforms having varied stimulation intensities to at least one electrode located proximate to nervous tissue of interest. A parameter defines the candidate stimulation waveforms is changed to vary the stimulation intensity. The method identifies a first candidate stimulation waveform that induces a paresthesia-abatement effect, while continuing to induce a select analgesic effect. The method further identifies a second candidate stimulation waveform that does not induce the select analgesic effect. The method sets a stimulation therapy based on the first and second candidate stimulation waveforms.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/978,664, filed Dec. 22, 2015, entitled “System and Method to ManagingStimulation of Select A-Beta Fiber Components,” which is incorporatedherein by reference.

BACKGROUND OF THE INVENTION

Spinal cord stimulation (SCS) is used to treat a wide range of chronicneuropathic pain conditions by delivering electrical stimulation toselect portions of the spinal cord. In the past, SCS therapy has beenproposed in which a tonic therapy is defined by single pulses have aselect pulse width, frequency and intensity. By way of example, tonictherapies have been proposed to manage cervical and lumbar pain. Thepulse width, frequency and intensity may be changed, along withelectrode configuration and placement on the spinal column in connectionwith pain relief for individual patients.

NS systems are devices that generate electrical pulses and deliver thepulses to nervous tissue to treat a variety of disorders. For example,spinal cord stimulation has been used to treat chronic and intractablepain. Another example is deep brain stimulation, which has been used totreat movement disorders such as Parkinson's disease and affectivedisorders such as depression. While a precise understanding of theinteraction between the applied electrical energy and the nervous tissueis not fully appreciated, it is known that application of electricalpulses to certain regions or areas of nervous tissue can effectivelyreduce the number of pain signals that reach the brain. For example,applying electrical energy to the spinal cord associated with regions ofthe body afflicted with chronic pain can induce “paresthesia” (asubjective sensation of numbness or tingling) in the afflicted bodilyregions.

SCS therapy, delivered via epidurally implanted electrodes, is a widelyused treatment for chronic intractable neuropathic pain of differentorigins. Traditional tonic therapy evokes paresthesia covering painfulareas of a patient. During SCS therapy calibration, the paresthesia isidentified and localized to the painful areas by the patient inconnection with determining correct electrode placement.

Recently, new stimulation configurations such as burst stimulation andhigh frequency stimulation, have been developed, in which closely spacedhigh frequency pulses are delivered to the spinal cord in a manner thatdoes not generate paresthesias for the majority of patients, but stillaffords a therapeutic result. Neuropathic pain may result from lesionsor diseases affecting the peripheral or central regions of thesomatosensory system, and is difficult to treat. The first spinal cordstimulator as a treatment for neuropathic pain was implanted by Shealyin 1967, which was based on the gate-control theory proposed by Melzackand Wall (1965). The gate-control theory proposed that intrinsicactivation of large diameter A-beta (A.beta.) fibers blocks or inhibitsthe transmission of noxious stimuli to the brain via an inhibitoryinterneuron. It has been shown that electrical stimulation also mayactivate the large diameter A-beta fibers with the same result. TheA-beta fibers transmit information from the peripheral nervous systemthrough the dorsal root ganglion (DRG) before entering and projectingalong the dorsal column.

Recent clinical evidence suggests that kilohertz frequency (about 10kHz) spinal cord stimulation (KHFSCS) and burst spinal cord stimulation(SCS) can produce paresthesia-free analgesia (relief from pain). Whileevidence exists that KHFSCS or burst SCS provides an effectiveneuromodulation therapy for patients with chronic pain, little is knownabout the potential therapeutic mechanisms of action.

A need remains for methods and systems to manage neuromodulation therapyto produce paresthesia free analgesia.

SUMMARY

In accordance with one embodiment a computer implemented method isprovided for managing neural stimulation therapy. The method comprisesunder control of one or more processors configured with programinstructions. The method delivers a series of candidate stimulationwaveforms having varied stimulation intensities to at least oneelectrode located proximate to nervous tissue of interest. A parameterdefines the candidate stimulation waveforms is changed to vary thestimulation intensity. The method identifies a first candidatestimulation waveform that induces a paresthesia-abatement effect, whilecontinuing to induce a select analgesic effect. The method furtheridentifies a second candidate stimulation waveform that does not inducethe select analgesic effect. The method sets a stimulation therapy basedon the first and second candidate stimulation waveforms.

Optionally, the second candidate stimulation waveform may exhibit astimulation intensity that blocks large and medium A-beta fibers thatwould otherwise induce paresthesia and analgesic effects, respectively.The stimulation therapy may block the large A-beta fibers havingdiameters of approximately 11.0-13.0 μm and may activate medium A-betafibers having diameters of approximately 6.0-11.0 μm. The candidatestimulation waveform may correspond to a high frequency stimulationwaveform or a burst stimulation waveform for spinal cord stimulation(SCS). The method further comprises delivering tonic SCS pulses duringthe stimulation therapy in combination with the high frequencystimulation waveform or burst stimulation waveform. The method mayutilize current steering to direct the tonic SCS pulses to dermatomes ofinterest.

Optionally, the stimulation therapy includes first and secondstimulation modalities. The method further comprises delivering thefirst and second stimulation modalities from different first and secondelectrode combinations. The method may comprise sensing evoked compoundaction potential (ECAP) signals, applying a narrow band-pass filter tothe ECAP signals to filter out stimulation artifacts from KHFSCS orburst SCS candidate waveforms, performing a fast Fourier transform tothe ECAP signals after the filtering operation and the identifyingoperations including analyzing the ECAP signals in a frequency domain.

Optionally, the analyzing includes determining a parameter settingassociated with the stimulation therapy that yields ECAP signals thatfit select profiles. The setting operation sets the stimulation therapyto have an intensity I based on the following equation:I=TH_(PF)+k*(TH_(U)−RH_(PF)), where k represents a constant, whereTH_(PF) represents a first intensity level corresponding to aparesthesia-abatement threshold and TH_(U) represents a second intensitylevel corresponding to an analgesic upper threshold.

In accordance with one embodiment, a system is provided for managingneural stimulation therapy. The system comprises a lead having at leastone stimulation electrode. The lead is configured to be implanted at atarget position proximate to nervous tissue of interest. The systemfurther comprises an implantable pulse generator (IPG) coupled to thelead. The IPG is configured to deliver a series of candidate stimulationwaveforms having varied stimulation intensities to at least oneelectrode located proximate to nervous tissue of interest, wherein aparameter defining the candidate stimulation waveforms is changed tovary the stimulation intensity. The IPG identifies a first candidatestimulation waveform that induces a paresthesia-abatement effect, whilecontinuing to induce a select analgesic effect. The IPG furtheridentifies a second candidate stimulation waveform that does not inducethe select analgesic effect. The IPG sets a stimulation therapy based onthe first and second candidate stimulation waveforms.

Optionally, the first candidate stimulation waveform exhibits astimulation intensity that blocks large diameter A-beta fibers thatwould otherwise induce a paresthesia effect. The second candidatestimulation waveform exhibits a stimulation intensity that blocks largeand medium diameter A-beta fibers that would otherwise induceparesthesia and analgesic effects, respectively. The target stimulationtherapy blocks the large A-beta fibers having diameters of approximately11.0-13.0 μm and activates medium A-beta fibers having diameters ofapproximately 6.0-11.0 μm. The candidate stimulation waveformcorresponds to a high frequency stimulation waveform or a burststimulation waveform for spinal cord stimulation (SCS).

Optionally, the IPG further delivers, as the stimulation therapy, tonicSCS pulses in combination with burst SCS waveforms or kilohertzfrequency SCS. The stimulation therapy represents a series of pulsebursts separated by quiescent periods, and the tonic SCS pulses aredelivered during the quiescent periods.

The IPG further senses sensory evoked compound action potential (ECAP)signals from the nervous tissue of interest and may analyze the ECAPsignals for ECAP activity data to identify first and second components.The first component may be indicative of ECAP activity of large diameterA-beta fibers. The second component may be indicative of ECAP activityof medium diameter A-beta fibers. The setting operation may be based onthe first and second components of the activity data.

The IPG may determine a parameter setting associated with thestimulation therapy that yields ECAP activity data for which the firstand second components fit within a select profile. The IPG sets thestimulation therapy to have an intensity I based on the followingequation: I=TH_(PF)+k*(TH_(U)−RH_(PF)), where k represents a constant,TH_(PF) represents a first intensity level corresponding to aparesthesia-abatement threshold, and TH_(U) represents a secondintensity level corresponding to an analgesic upper threshold.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an NS system that generates electrical pulses forapplication to tissue of a patient according to one embodiment.

FIG. 2A depicts stimulation portions for inclusion at the distal end oflead in accordance to embodiments herein.

FIG. 2B depicts stimulation portions for inclusion at the distal end oflead in accordance to embodiments herein.

FIG. 2C depicts stimulation portions for inclusion at the distal end oflead in accordance to embodiments herein.

FIG. 3 illustrates simulation results obtained by Arle et al., showingthe firing rate of A-beta fibers as a function of fiber diameter andstimulation frequency, pulse width, and amplitude (voltage) inaccordance with embodiments herein.

FIG. 4A illustrates a process for identifying thresholds for neuralstimulation therapy in accordance with embodiments herein.

FIG. 4B illustrates a process for identifying thresholds for neuralstimulation therapy in accordance with embodiments herein.

FIG. 4C illustrates the process for setting a stimulation therapy basedupon thresholds identified in accordance with embodiments herein.

FIG. 5A illustrates hybrid therapies that may be delivered in accordancewith embodiments herein.

FIG. 5B illustrates hybrid therapies that may be delivered in accordancewith embodiments herein.

FIG. 6 illustrates an example of a portion of a lead that may beutilized in accordance with embodiments herein.

FIG. 7 illustrates a method to determine a stimulation therapy throughanalysis of evoked compound action potentials (ECAP) signals generatedin response to candidate stimulation waveforms in accordance withembodiments herein.

FIG. 8 illustrates examples of frequency spectrums that may be exhibitedby ECAP signals when converted to the frequency domain in accordancewith embodiments herein.

FIG. 9 illustrates a functional block diagram of an embodiment of anelectronic control unit (ECU) 900 that is operated in accordance withthe processes described herein.

DETAILED DESCRIPTION

While multiple embodiments are described, still other embodiments of thedescribed subject matter will become apparent to those skilled in theart from the following detailed description and drawings, which show anddescribe illustrative embodiments of disclosed inventive subject matter.As will be realized, the inventive subject matter is capable ofmodifications in various aspects, all without departing from the spiritand scope of the described subject matter. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

The nervous system is comprised of the central nervous system (CNS) andthe peripheral nervous system (PNS). The CNS contains the brain andspinal cord. The PNS is comprised mainly of mixed nerves, which areenclosed bundles of the long fibers or axons that connect the CNS toevery other part of the body. Two types of nerve fibers in a mixed nerveinclude: sensory nerve fibers (afferent fibers sending informationtowards the brain) and motor nerve fibers (efferent fibers sendinginformation from the brain). Sensory neurons transmit information fromthe environment, such as pain and motor neurons that mediate voluntaryand involuntary movement.

In general, the peripheral nerve fibers may be classified into threetypes of nerve fibers based on the nerve fiber diameter and conductionvelocity, namely A-, B- and C-fibers. A-fibers have large diameters,high conduction velocities, are myelinated, and are further subdividedby size and conduction velocity as A-alpha, A-beta, A-gamma and A-deltafibers. By way of example, the fast conduction velocity of the A-alphafibers may be on the order of 80-120 m/s, and the A-alpha fibers may beon average 13-20 μm in diameter. B-fibers have diameters of about 3.mu.m and conduction velocities of 3-15 m/s. C-fibers are small neuronswith slow conduction velocities and are not myelinated. The A-betafibers represent type II sensory fibers that have size generally rangingbetween 5.0-13.0 μm, and convey action potential (AP) signals atvelocities between 30-70 m/s.

It has been shown that high-frequency kilohertz spinal cord stimulation(KHFSCS) or burst SCS stimulation provides an effective neuromodulationtherapy for patients with chronic pain. Recent computational modelingwork by Arle et al. (Arle J E, Mei L, Carlson K W, and Shils J L. “Highfrequency stimulation of dorsal column axons: potential underlyingmechanism of paresthesia-free neuropathic pain”. Poster at InternationalNeuromodulation Society Conference. 2015) explains that KHFSCS and burstSCS may work by blocking the large diameter A-beta fibers (11.7-13.0 μmdiameter) that transmit the sensation of vibration (paresthesia), whileactivating medium diameter A-beta fibers (6.1-11.1 μm diameter) thatgenerate analgesia via the gate-control theory.

FIG. 3 illustrates simulation results obtained by Arle et al., showingthe firing rate of A-beta fibers as a function of fiber diameter andstimulation frequency, pulse width, and amplitude (voltage). FIG. 3plots the neural firing rate (Hz) (along the vertical y-axis) versusfiber diameter (μm) (along the receding z-axis) versus stimulationfrequency (Hz) (along the horizontal X axis). For each stimulation pulsewidth (pw=10 μm, 50 μm, 70 μm, or 90 μm), there are six panels showingthe neural firing or action potential activity for varied stimulationamplitude (0.5 to 5 V). At low stimulation amplitudes (about 0.5V),large fibers (>11 μm) fired only with high stimulation frequencies of6-10 kHz (depending on the pulse width). As stimulation strength wasincreased (about 1 V), neural firing of medium diameter fibers (6-11 μm)increased, and neural firing of large diameter fibers was observed atlower frequencies (<6 kHz). Most importantly, as stimulation strengthwas increased still further (2-5 V), the firing rate of large fibersdecreased or ceased completely with high frequency stimulation (4-10kHz), while medium fibers continued to fire (exhibit action potentialactivity).

In accordance with embodiments herein, methods and systems are describedthat select and manage stimulation parameters to entirely ofsubstantially block large diameter A-beta fibers that otherwise transmitparesthesia (thereby achieving a paresthesia-abatement effect), whilecontinuing to activate medium diameter A.beta. fibers to achieve adesired analgesia effect.

In accordance with embodiments herein, a programmer and/or NS system isprovided that is configured to select therapy parameters that define anon-paresthesia therapy that achieves a desired analgesic effect. Afterimplantation of the NS system, an intraoperative programming session maybe conducted while the patient is awake. For example, the NS systemand/or programmer may step through a series of candidate stimulationwaveforms having varied stimulation intensities, determined by varyingone or more parameters that define the candidate stimulation waveform.At each step in the process, the patient may be queried as to whetherthe patient experiences paresthesia, pain or another sensation. From thepatient feedback, while testing different candidate stimulationwaveforms, at least first and second candidate stimulation waveforms areidentified. For example, the first candidate stimulation waveform isidentified that induces a paresthesia-abatement effect (e.g. the patientexperiences no or very limited paresthesia), while still experiencing aselect analgesic effect (e.g. the patient experiences no pain orrelatively small amount of pain at the region of interest). The secondcandidate stimulation waveform is identified (while receiving adifferent, higher stimulation intensity), at which the select analgesiceffect is no longer experienced. The candidate stimulation waveforms arethen used to set the stimulation therapy.

Optionally, the stimulation therapy may be set while the patient isunconscious. In accordance with embodiments herein, methods and systemsmeasure evoked compound action potential (ECAP) signals that areconveyed by the A-beta fibers in response to each candidate stimulationwaveform. The ECAP signals are recorded and analyzed (automatically orthrough visual inspection) by the clinician, the NS system or anexternal programmer device. Based on the analysis of the ECAP signals,the first and second candidate stimulation waveforms are identified, andbased thereon, the stimulation therapy is set.

FIG. 1 depicts an NS system 100 that generates electrical pulses forapplication to tissue of a patient according to one embodiment. Forexample, the NS system 100 may be adapted to stimulate spinal cordtissue, peripheral nervous tissue, deep brain tissue, cortical tissue,cardiac tissue, digestive tissue, pelvic floor tissue, or any othersuitable nervous tissue of interest within a patient's body. The NSsystem 100 may be controlled to deliver various types of non-paresthesiatherapy, such as high frequency neurostimulation therapies, burstneurostimulation therapies and the like. High frequency neurostimulationincludes a continuous series of monophasic or biphasic pulses that aredelivered at a predetermined frequency (such as 2-10K). Burstneurostimulation includes short sequences of monophasic or biphasicpulses, where each sequence is separated by a quiescent period. By wayof example, the pulses within each burst sequence may be delivered withan intraburst frequency of about 500 Hz. In general, non-paresthesiatherapies include a continuous, repeating or intermittent pulse sequencedelivered at a frequency and amplitude configured to avoid inducing (orintroduce a very limited) paresthesia.

The NS system 100 may represent a closed loop neurostimulation device,where the new device is configured to provide real-time sensingfunctions for A-beta action potential (APs) from various locations suchas a dorsal root ganglion (DRG) lead, a dorsal column lead and the like.The configuration of the lead sensing electrodes that sense actionpotentials from the A-beta fibers may be varied depending on theneuronal anatomy of the sensing site(s) of interest. The size and shapeof electrodes is varied based on the implant location, such as thedorsal root (DR) or DRG, or the location on the implant spinal column.By way of example only, a laminectomy procedure may be used for PENTA orother paddle leads placed in SC epidural space, in order to obtainaccurate action potential signals indicative of pain from the A-betafiber. The electronic components within the NS system 100 are designedwith both stimulation and sensing capabilities, including alternativenon-paresthesia stimulation therapy, such as burst mode, high frequencymode and the like. The NS system 100 detects and characterizes A-betafiber action potential signals. In one embodiment, one lead stimulatesthe dorsal column, the second lead senses from DRG or DR, vice versa. Inanother embodiment, the lead can stimulate DRG or DR or SC and sensefrom the same stimulation location.

The NS system 100 includes an implantable pulse generator (IPG) 150 thatis adapted to generate electrical pulses for application to tissue of apatient. The IPG 150 typically comprises a metallic housing or can 159that encloses a controller 151, pulse generating circuitry 152, acharging coil 153, a battery 154, a far-field and/or near fieldcommunication circuitry 155, battery charging circuitry 156, switchingcircuitry 157, memory 158 and the like. The controller 151 typicallyincludes a microcontroller or other suitable processor for controllingthe various other components of the device. Software code (programinstructions) is typically stored in memory of the IPG 150 for executionby the microcontroller or processor to control the various components ofthe device.

The IPG 150 may comprise a separate or an attached extension component170. If the extension component 170 is a separate component, theextension component 170 may connect with the “header” portion of the IPG150 as is known in the art. If the extension component 170 is integratedwith the IPG 150, internal electrical connections may be made throughrespective conductive components. Within the IPG 150, electrical pulsesare generated by the pulse generating circuitry 152 and are provided tothe switching circuitry 157. The switching circuitry 157 connects tooutputs of the IPG 150. Electrical connectors (e.g., “Bal-Seal”connectors) within the connector portion 171 of the extension component170 or within the IPG header may be employed to conduct variousstimulation pulses. The terminals of one or more leads 110 are insertedwithin connector portion 171 or within the IPG header for electricalconnection with respective connectors. Thereby, the pulses originatingfrom the IPG 150 are provided to the leads 110. The pulses are thenconducted through the conductors of the lead 110 and applied to tissueof a patient via stimulation electrodes 121 that are coupled to blockingcapacitors. Any suitable known or later developed design may be employedfor connector portion 171.

The stimulation electrodes 121 may be positioned along a horizontal axis102 of the lead 110, and are angularly positioned about the horizontalaxis 102 so the stimulation electrodes 121 do not overlap. Thestimulation electrodes 121 may be in the shape of a ring such that eachstimulation electrode 121 continuously covers the circumference of theexterior surface of the lead 110. Each of the stimulation electrodes 121are separated by non-conducting rings 112, which electrically isolateeach stimulation electrode 121 from an adjacent stimulation electrode121. The non-conducting rings 112 may include one or more insulativematerials and/or biocompatible materials to allow the lead 110 to beimplantable within the patient. Non-limiting examples of such materialsinclude polyimide, polyetheretherketone (PEEK), polyethyleneterephthalate (PET) film (also known as polyester or Mylar),polytetrafluoroethylene (PTFE) (e.g., Teflon), or parylene coating,polyether bloc amides, polyurethane. The stimulation electrodes 121 maybe configured to emit the pulses in an outward radial directionproximate to or within a stimulation target. Additionally oralternatively, the stimulation electrodes 121 may be in the shape of asplit or non-continuous ring such that the pulse may be directed in anoutward radial direction adjacent to the stimulation electrodes 121. Thestimulation electrodes 121 SCS tonic deliver high frequency and/or burststimulation waveforms as described herein. The electrodes 121 may alsosense action potential signals for a data collection cluster.Optionally, the delivering operation may deliver the one stimulationwaveform to a first sub-set of the electrodes and another stimulationwaveform to a second sub-set of the electrodes, where the first andsecond sub-sets have at least one unique electrode relative to eachother.

Optionally, the electrodes may include microelectrodes locatedimmediately adjacent to the A-beta fibers. The method may sense A-betafiber sensory action activity directly at the microelectrodes.

The lead 110 may comprise a lead body 172 of insulative material about aplurality of conductors within the material that extend from a proximalend of lead 110, proximate to the IPG 150, to its distal end. Theconductors electrically couple a plurality of the stimulation electrodes121 to a plurality of terminals (not shown) of the lead 110. Theterminals are adapted to receive electrical pulses and the stimulationelectrodes 121 are adapted to apply the pulses to the stimulation targetof the patient. Also, sensing of physiological signals may occur throughthe stimulation electrodes 121, the conductors, and the terminals. Itshould be noted that although the lead 110 is depicted with fourstimulation electrodes 121, the lead 110 may include any suitable numberof stimulation electrodes 121 (e.g., less than four, more than four) aswell as terminals, and internal conductors. Additionally oralternatively, various sensors (e.g., a position detector, a radiopaquefiducial) may be located near the distal end of the lead 110 andelectrically coupled to terminals through conductors within the leadbody 172.

Although not required for any embodiments, the lead body 172 of the lead110 may be fabricated to flex and elongate upon implantation oradvancing within the tissue (e.g., nervous tissue) of the patienttowards the stimulation target and movements of the patient during orafter implantation. By fabricating the lead body 172, according to someembodiments, the lead body 172 or a portion thereof is capable ofelastic elongation under relatively low stretching forces. Also, afterremoval of the stretching force, the lead body 172 may be capable ofresuming its original length and profile. For example, the lead body maystretch 10%, 20%, 25%, 35% or even up or above to 50% at forces of about0.5, 1.0, and/or 2.0 pounds of stretching force. Fabrication techniquesand material characteristics for “body compliant” leads are disclosed ingreater detail in U.S. Provisional Patent Application No. 60/788,518,entitled “Lead Body Manufacturing,” which is expressly incorporatedherein by reference.

FIGS. 2A-2C respectively depict stimulation portions 200, 225, and 250for inclusion at the distal end of lead 110. Stimulation portion 200depicts a conventional stimulation portion of a “percutaneous” lead withmultiple ring electrodes. Stimulation portion 225 depicts a stimulationportion including several segmented electrodes. Example fabricationprocesses are disclosed in U.S. patent application Ser. No. 12/895,096,entitled, “METHOD OF FABRICATING STIMULATION LEAD FOR APPLYINGELECTRICAL STIMULATION TO TISSUE OF A PATIENT,” which is incorporatedherein by reference. Stimulation portion 250 includes multiple planarelectrodes on a paddle structure. Returning to FIG. 1, forimplementation of the components within the IPG 150, a processor andassociated charge control circuitry for an IPG is described in U.S. Pat.No. 7,571,007, entitled “SYSTEMS AND METHODS FOR USE IN PULSEGENERATION,” which is expressly incorporated herein by reference.Circuitry for recharging a rechargeable battery (e.g., battery chargingcircuitry 156) of an IPG using inductive coupling and external chargingcircuits are described in U.S. Pat. No. 7,212,110, entitled “IMPLANTABLEDEVICE AND SYSTEM FOR WIRELESS COMMUNICATION,” which is expresslyincorporated herein by reference.

An example and discussion of “constant current” pulse generatingcircuitry (e.g., pulse generating circuitry 152) is provided in U.S.Patent Publication No. 2006/0170486 entitled “PULSE GENERATOR HAVING ANEFFICIENT FRACTIONAL VOLTAGE CONVERTER AND METHOD OF USE,” which isexpressly incorporated herein by reference. One or multiple sets of suchcircuitry may be provided within the IPG 150. Different burst and/orhigh frequency pulses on different stimulation electrodes 121 may begenerated using a single set of the pulse generating circuitry 152 usingconsecutively generated pulses according to a “multi-stimset program” asis known in the art. Complex pulse parameters may be employed such asthose described in U.S. Pat. No. 7,228,179, entitled “Method andapparatus for providing complex tissue stimulation patterns,” andInternational Patent Publication Number WO 2001/093953 A1, entitled“NEUROMODULATION THERAPY SYSTEM,” which are expressly incorporatedherein by reference. Alternatively, multiple sets of such circuitry maybe employed to provide pulse patterns (e.g., tonic stimulation waveform,burst stimulation waveform) that include generated and deliveredstimulation pulses through various stimulation electrodes of one or moreleads 121 as is also known in the art. Various sets of parameters maydefine the pulse characteristics and pulse timing for the pulses appliedto the various stimulation electrodes 121. Although constant currentpulse generating circuitry is contemplated for some embodiments, anyother suitable type of pulse generating circuitry may be employed suchas constant voltage pulse generating circuitry.

The controller 151 delivers a series of candidate stimulation waveformshaving varied stimulation intensities to at least one electrode locatedproximate to nervous tissue of interest, wherein a parameter definingthe candidate stimulation waveforms is changed to vary the stimulationintensity. While stepping through different intensity levels, thecontroller 151 identifies a first candidate stimulation waveform thatinduces a paresthesia-abatement effect, while continuing to induce aselect analgesic effect. While stepping through different intensitylevels, the controller 151 identifies a second candidate stimulationwaveform that does not induce the select analgesic effect. Thecontroller 151 sets a stimulation therapy based on, among other things,the first and second candidate stimulation waveforms.

The controller 151 iteratively repeats the delivering and sensingoperations for a group of candidate stimulation waveforms. In accordancewith certain embodiments, patient feedback is utilized toidentify/classify the candidate stimulation waveforms to identify one ormore candidate waveform that achieves a desired paresthesia-abatementeffect while maintaining a select analgesic effect. The patient feedbackmay also be utilized to identify/classify the candidate stimulationwaveforms to identify one or more candidate waveforms that are no longerable to maintain the select analgesic effect.

Optionally, the controller 151 may perform signal analysis upon ECAPsignals to automatically identify the candidate stimulation waveforms(e.g. based on profiles and frequency discrimination after convertingthe ECAP signals through Fast Fourier transforms to the frequencydomain). The analyzing operation may utilize profiles by analyzing afeature of interest from a morphology of the ECAP signal over time,counting a number of occurrences of the feature of interest that occurwithin the ECAP signal over a predetermined duration, and generating theactivity data based on the number of occurrences of the feature ofinterest.

The therapy parameters define at least one of a burst stimulationwaveform or a high frequency stimulation waveform. The controller 151may determine whether an energy content of the ECAP signal in selectfrequency clusters falls below a threshold or within an acceptable range(representing one type of profile), thereby indicating aparesthesia-abatement effect (e.g. that no pain or an acceptable lowlevel of pain) is experienced by the patient.

Memory 158 stores software (program instructions) to control operationof the controller 151. The memory 158 also stores ECAP signals, therapyparameters, ECAP activity level data, sensory scores, pain scales andthe like. For example, the memory 158 may save ECAP activity level datafor various different candidate waveforms as applied over a short orextended period of time. A collection of ECAP activity level data isaccumulated for different candidate waveforms and may be compared toidentify high, low and acceptable amounts of sensory activity for theA-beta fibers that result from different candidate waveforms. The memory158 stores a pain-activity data relation defining a relation betweenenergy content of the ECAP signals in select frequency clusters andsensory scores indicative of pain experienced by a patient.

A controller device 160 may be implemented to charge/recharge thebattery 154 of the IPG 150 (although a separate recharging device couldalternatively be employed) and to program the IPG 150 on the pulsespecifications while implanted within the patient. Although, inalternative embodiments separate programmer devices may be employed forcharging and/or programming the NS system 100. The controller device 160may be a processor-based system that possesses wireless communicationcapabilities. Software may be stored within a non-transitory memory ofthe controller device 160, which may be executed by the processor tocontrol the various operations of the controller device 160. A “wand”165 may be electrically connected to the controller device 160 throughsuitable electrical connectors (not shown). The electrical connectorsmay be electrically connected to a telemetry component 166 (e.g.,inductor coil, RF transceiver) at the distal end of wand 165 throughrespective wires (not shown) allowing bi-directional communication withthe IPG 150. Optionally, in some embodiments, the wand 165 may compriseone or more temperature sensors for use during charging operations.

The user may initiate communication with the IPG 150 by placing the wand165 proximate to the NS system 100. Preferably, the placement of thewand 165 allows the telemetry system of the wand 165 to be aligned withthe far-field and/or near field communication circuitry 155 of the IPG150. The controller device 160 preferably provides one or more userinterfaces 168 (e.g., touchscreen, keyboard, mouse, buttons, or thelike) allowing the user to operate the IPG 150. The controller device160 may be controlled by the user (e.g., doctor, clinician) through theuser interface 168 allowing the user to interact with the IPG 150. Theuser interface 168 may permit the user to move electrical stimulationalong and/or across one or more of the lead(s) 110 using differentstimulation electrode 121 combinations, for example, as described inU.S. Patent Application Publication No. 2009/0326608, entitled “METHODOF ELECTRICALLY STIMULATING TISSUE OF A PATIENT BY SHIFTING A LOCUS OFSTIMULATION AND SYSTEM EMPLOYING THE SAME,” which is expresslyincorporated herein by reference.

Also, the controller device 160 may permit operation of the IPG 150according to one or more therapies to treat the patient. Each therapymay include one or more sets of stimulation parameters of the pulseincluding pulse amplitude, pulse width, pulse frequency or inter-pulseperiod, pulse repetition parameter (e.g., number of times for a givenpulse to be repeated for respective stimset during execution ofprogram), biphasic pulses, monophasic pulses, etc. The IPG 150 modifiesits internal parameters in response to the control signals from thecontroller device 160 to vary the stimulation characteristics of thestimulation pulses transmitted through the lead 110 to the tissue of thepatient. NS systems, stimsets, and multi-stimset programs are discussedin PCT Publication No. WO 01/93953, entitled “NEUROMODULATION THERAPYSYSTEM,” and U.S. Pat. No. 7,228,179, entitled “METHOD AND APPARATUS FORPROVIDING COMPLEX TISSUE STIMULATION PATTERNS,” which are expresslyincorporated herein by reference.

FIGS. 4A-4C illustrate processes for selecting and managing (e.g. burstand/or high frequency) stimulation of nervous tissue of a patient inaccordance with embodiments herein. The operations of FIGS. 4A-4C may beimplemented by one or more processors, such as within a controller, animplantable pulse generator, external programmer, another externaldevice and the like. The IPG, external programmer or other externaldevice are coupled to a lead having at least one stimulation electrodethat is implanted at a target position proximate to nervous tissue ofinterest.

FIGS. 4A-4B illustrate a process for identifying thresholds for neuralstimulation therapy in accordance with embodiments herein. At 402, thecontroller 151 (FIG. 1) delivers a candidate stimulation waveform to atleast one electrode located proximate to nervous tissue of interest. Thecandidate stimulation waveform is defined by one or more parameters thatdetermine the stimulation intensity, among other things, associated withthe candidate stimulation waveform.

At 404, a patient sensory score is collected indicative of an effectinduced by the candidate stimulation waveform. For example, the patientmay indicate one or more ratings along one or more scales indicative ofvarious characteristics experienced by the patient. For example, thepatient may provide a rating that is indicative of an amount or degreeof paresthesia experienced in a physical region of interest associatedwith the nervous tissue of interest. The patient may also provide arating that is indicative of an amount or degree of pain experienced inthe region of interest. Additionally or alternatively, the patient mayprovide a rating indicative of an amount or degree of pleasure/analgesiaexperienced in the region of interest.

At 406, the controller 151 saves the sensory score and the correspondingtherapy parameter set. At 408, the controller determines whetheradditional candidate stimulation waveforms are to be tested. If so, flowbranches to 410. Otherwise, flow moves to 412. The decision at 408 isbased on various criteria. For example, the decision at 408 may be basedon the sensory scores assigned by the patient to prior candidatestimulation waveforms. More specifically, at 408, the branching criteriamay correspond to whether the patient has indicated that the presentcandidate stimulation waveform has induced a paresthesia-abatementeffect while continuing to induce a select analgesic effect. Forexample, the patient may indicate, through the sensory score, thatlittle or no paresthesia is felt, and that little or no pain is felteither. When little or no paresthesia or pain are experienced, this isinterpreted as a strong indicator that the present candidate stimulationwaveform is supplying a stimulation intensity that is sufficient toblock larger diameter A.beta. fibers, but continues to excite mediumsize A. beta. fibers.

At 408, when the sensory score indicates that the patient is stillexperiencing paresthesia, the controller 151 may determine thatadditional candidate stimulation waveforms should be tested.Accordingly, flow moves to 410. At 410, one or more therapy parametersare changed within a therapy parameter set. For example, the operationat 410 may change one or more of pulse amplitude, pulse width, pulsefrequency or inter-pulse period, pulse repetition parameter (e.g.,number of times for a given pulse to be repeated for respective stimsetduring execution of program), biphasic pulses, monophasic pulses, etc.The candidate stimulation waveform and therapy may represent a KHFSCSwaveform/therapy or burst SCS waveform/therapy. When using KHFSCSstimulation waveforms and therapy, it may be desirable to utilize pulsewidths greater than or equal to 50 μm s, as pulse widths below 50 μm smay not provide adequate block of large diameter fibers.

The operations at 402-410 are repeated for a first series of candidatestimulation waveforms in order to vary stimulation intensity by changingone or more of the therapy parameters. The operations at 402-410 arerepeated until a first candidate stimulation waveform is identified thatinduces a paresthesia-abatement effect, while continuing to induce aselect analgesic effect. When the controller 151 determines that noadditional testing is warranted, namely that a candidate stimulationwaveform is identified that achieves the desired combination ofparesthesia abatement and analgesia, flow moves to 412. At 412, thelevel for one or more parameters of interest (also referred to as atherapy parameter set or TPS) is recorded as the paresthesia freethreshold (TH_(PF)). Thereafter, flow advances to FIG. 4B.

The process of FIG. 4B steps through a second series of candidatestimulation waveforms to identify a second candidate stimulationwaveform that induces another effect of interest. The second series ofcandidate stimulation waveforms corresponds to a paresthesia free“window”, in which little or no paresthesia is experienced. Thecandidate stimulation waveforms delivered in connection with FIG. 4B areexpected to block the large diameter A. beta. fibers, and thus are notexpected to induce notable paresthesia. Instead, the candidatestimulation waveforms delivered in connection with FIG. 4B are used tosearch for a stimulation intensity that also blocks the medium diameterA.beta. fibers, thereby failing to provide an analgesia effect.

At 422, the controller 151 (FIG. 1) delivers a candidate stimulationwaveform to at least one electrode located proximate to nervous tissueof interest. The candidate stimulation waveform is set to have anintensity greater than the intensity associated with the paresthesiafree threshold TH_(PF).

At 424, another patient sensory score is collected indicative of aneffect induced by the candidate stimulation waveform. Again, the patientmay indicate one or more ratings along one or more scales indicative ofvarious characteristics experienced by the patient. For example, thepatient may provide a rating that is indicative of an amount or degreeof paresthesia, amount or degree of pain, and/or amount or degree ofpleasure experienced in the region.

At 426, the controller 151 saves the sensory score and the correspondingtherapy parameter set. At 428, the controller determines whetheradditional candidate stimulation waveforms are to be tested. If so, flowbranches to 430. Otherwise, flow moves to 432. The decision at 428 isbased on various criteria. For example, the decision at 428 may be basedon the sensory scores assigned by the patient to prior candidatestimulation waveforms. More specifically, at 428, the criteria maycorrespond to whether the patient has indicated that the presentcandidate stimulation waveform continues to induce a select analgesiceffect. For example, the patient may indicate, through the sensoryscore, that none, little, medium, or substantial pain is felt. Whenlittle or no pain is experienced, this is interpreted as an indicatorthat the present candidate stimulation waveform is supplying astimulation intensity that is still sufficient to excite medium sizeA.beta. fibers. When the sensory score indicates that medium orsubstantial pain is felt, this is interpreted as an indication that thepresent candidate stimulation waveform is supplying a stimulationintensity that has begun to block the medium-size A.beta. fibers, and assuch no longer provides a desired analgesic effect.

At 428, when the sensory score indicates that the patient still is notexperiencing pain, the controller 151 may determine that additionalcandidate stimulation waveforms should be tested. Accordingly, flowmoves to 430. At 430, one or more therapy parameters are changed withina therapy parameter set. Alternatively, at 428, the sensory score mayindicate that the patient is experiencing an amount of pain sufficientto indicate that the candidate stimulation waveform is entirely orsubstantially blocking the medium-size A.beta. fibers.

The operations at 422-430 are repeated for a series of candidatestimulation waveforms in order to vary stimulation intensity by changingone or more of the therapy parameters. The operations at 422-430 arerepeated until a second candidate stimulation waveform is identifiedthat no longer induces a select analgesic effect. When the controller151 determines that no additional testing is needed, namely that acandidate stimulation waveform is identified that has ceased to providethe select analgesic effect, flow moves to 432. At 432, the level forone or more parameters of interest is recorded as the analgesia upperthreshold (TH_(U)). Thereafter, flow moves to FIG. 4C.

Optionally, the adjustment of pulse amplitude, pulse width and the like,at 410 (FIG. 4A) and 430 (FIG. 4B) may be implemented alone or incombination with adjustment of another therapy parameter, such as thenumber or pattern of excited electrodes, frequency and/or intra-burstfrequency. For example, when utilizing KHFSCS stimulation therapies, theoperations of FIGS. 4A-4B may carried out in connection with adjustingfrequency each time a therapy parameter is changed at 410 and 430. Byadjusting the frequency during successive attempts of candidatestimulation waveforms, the process provides a frequency scan search overa frequency range of interest (e.g., 10 kHz down to 3 kHz). Thefrequency scan search may be performed for determining a select (e.g.,optimized) analgesia effect that limits/minimizes energy usage whilemaintaining paresthesia-free stimulation.

Additionally or alternatively, when utilizing burst SCS stimulationtherapies, the operations of FIGS. 4A-4B may be repeated by adjustingthe intra-burst frequency as one parameter changed at 410 and 430. As afurther example, when adjusting frequency and/or intra-burst frequency,in combination with pulse width and/or pulse amplitude, the order inwhich the parameters are adjusted may be varied. For example, a seriesof pulse amplitudes and/or pulse widths may be tested at each frequency(for KHFSCS) or tested at each intra-burst frequency (for burst SCS).Alternatively, a series of frequencies or intra-burst frequencies may betested at each pulse amplitude and/or pulse width. It is recognized thatvarious combinations of parameter levels may be tested in numerousorders and combinations.

In the present example, patients enter one or more rating on a sensoryscore as the primary type of feedback collected in connection with eachcandidate stimulation waveform. Optionally, one or more additional typesof feedback or tests may be performed in connection with each candidatestimulation waveform. The alternative types of feedback or tests wouldbe tailored to identify a degree of paresthesia and analgesic effect. Asexplained herein, one alternative type of test that may be appliedrepresents sensing ECAP signals and analyzing ECAP signals forcharacteristics of interest that are indicative of a desiredparesthesia-abatement effect and analgesic effect.

In the present example, the candidate stimulation waveforms aredelivered from one or more electrodes chosen to target a primary regionof interest in which a patient is experiencing pain or anotherphysiologic abnormality. Optionally, additional tests may be performed,such as utilizing alternative electrode combinations targeted to induceparesthesia-abatement and/or analgesic effects at other regions on apatient, other than the initial region of interest. For example, it maybe desirable to test alternative electrode configurations to targetother regions of interest when “secondary” regions of interest (e.g.,leg) are found to effect pain and other sensations experienced at aprimary region of interest (e.g., foot).

FIG. 4C illustrates the process for setting a stimulation therapy basedupon thresholds identified in accordance with embodiments herein. Forexample, the stimulation therapy may be based upon the first and secondcandidate stimulation waveforms identified in FIGS. 4A and 4B. At 450,the controller 151 identifies the stored parameter settings that wererecorded in connection with the characteristics of interest, such as inconnection with the paresthesia abatement threshold TH_(PF) andanalgesic upper threshold TH_(U). At 452, the controller determines arelationship to be used when calculating the stimulation therapy basedon the stored parameter settings. At 454, the controller 151 applies therelationship to obtain a stimulation therapy. By way of example, therelationship of interest may involve setting the stimulation therapy tohave a stimulation intensity I based on the following equation:I=TH_(PF)+k*(TH_(U)−TH_(PF)), wherein k represents a constant (e.g.,0.2-0.8), where TH_(PF) represents a first intensity level correspondingto a paresthesia-abatement threshold and TH_(U) represents a secondintensity level corresponding to an analgesic upper threshold.Optionally, alternative relationships may be used. Optionally, at 456, atest therapy stimulation may be delivered utilizing the parameterscalculated at 454 to confirm that a desired effect is induced.

In accordance with embodiments herein, the operations of FIGS. 4A-4Cprovide an algorithm to determine the paresthesia-free stimulationparameters for KHFSCS or burst SCS. The process of FIGS. 4A-4C determinea stimulation parameter set through various operations. First, thestimulation intensity is ramped up from a low starting value (0 V or 0mA) until the patient feels paresthesia. When the patient initiallyfeels paresthesia, this indicates initial activation of large diameterA.beta. fibers. Next, the stimulation intensity is increased furtheruntil paresthesia disappears, which is defined as theparesthesia-abatement threshold. The paresthesia-abatement thresholdrepresents a generally lower limit of stimulation intensity that blockslarge diameter A-beta fibers and concurrent activates medium diameterA-beta fibers. It is recognized that the paresthesia-abatement thresholdmay correspond to more than one stimulation intensity level within asmall range. For example, the threshold TH_(PF) may correspond to apoint at which the patient experiences a very small amount ofparesthesia. Alternatively, the threshold TH_(PF) may correspond to apoint at which the patient does not experience any paresthesia, referredto as a paresthesia-free effect or point.

Once the threshold TH_(PF) is found, subsequently, the process continuesto ramp up the stimulation intensity still further until pain reappears,which is defined as the analgesic upper threshold. The upper thresholdis the point at which the stimulation intensity blocks both the mediumand large diameter A-beta fibers from conveying non-pain inputs thatwould otherwise close the “gate” to the central nervous system frompainful inputs. When both medium and large diameter A-beta fibers areblocked from conveying non-pain inputs, a corresponding loss of theanalgesic effects of the SCS candidate stimulation waveforms occurs andthe gate-control theory can no longer be used to prevent transfer ofpain inputs to the central nervous system. The gate control theory ofpain generally indicates that an appropriate non-painful input closesone or more “gates” to painful input. The gates represent points ofentry to the central nervous system and, when closed, prevent painsensation from reaching the brain's sensory system. Therefore,accordingly to the gate control theory of pain, stimulation bynon-noxious input is able to suppress pain by preventing the pain inputfrom entering the central nervous system. The stimulation intensitiesbetween the paresthesia-abatement threshold and the upper thresholdinduce non-painful inputs in a manner that takes advantage of the gatecontrol theory. However, an upper limit exists as to the stimulationintensity that can be used to induce non-noxious inputs that close thegates to pain sensations. Stimulation intensities that exceed the upperthreshold do not close the gates of the central nervous system to pain.

Accordingly, in accordance with embodiments herein, theparesthesia-abatement threshold and upper threshold are used tocalculate values for one or more therapy parameters that manage astimulation therapy to avoid introducing undesirable levels ofparesthesia, while taking advantage of the gate control theory to blockentry of pain to the central nervous system.

In the foregoing example, the stimulation therapy represented a KHFSCStherapy or a burst SCS therapy.

FIGS. 5A and 5B illustrate hybrid therapies that may be delivered inaccordance with embodiments herein. FIG. 5A illustrates a hybrid therapy502 that includes a paresthesia-free KHFSCS waveform 504 combined withlow-frequency tonic SCS waveform 506 (e.g., 30-100 Hz) to achieve adesired level of (e.g. optimize) analgesia coverage in the painful bodydermatomes. The KHFSCS and tonic SCS waveforms 504 and 506 are combinedto be delivered together simultaneously. The KHFSCS waveform 504includes a repeating series of pulses having positive and negativephases 510 and 512, where successive pulses are separated by a quiescentperiod 514. The tonic SCS waveform 506 may be timed to deliver pules 508therein during the quiescent period 514 in the KHFSCS waveform 504.Optionally, the pulse 508 in the tonic SCS waveform 506 may be deliveredduring one or more of the pulses in the KHFSCS waveform 504. The KHFSCSwaveform 504 and tonic SCS waveform 506 may be delivered through thesame electrode combinations or delivered from different combinations ofelectrodes.

FIG. 5B illustrates a hybrid therapy 522 that includes a burst SCSwaveform 524 combined with a low-frequency tonic SCS waveform 526 (e.g.30-100 Hz) to achieve a desired level (e.g. optimize) of analgesiccoverage in the painful body dermatomes. The burst SCS and tonic SCSwaveforms 524 and 526 are combined to be delivered simultaneously. Theburst SCS waveform 524 includes a series of burst trains 525 separatedby a quiescent period 527. The tonic SCS waveform 526 may be timed todeliver pulses 528 therein during the quiescent period 527 in the burstSCS waveform 524. Given that the inter-burst frequency between bursttrains 525 is in approximately the same range as the tonic frequency,the tonic pulses 528 may be delivered between each of (or simultaneouswith) the burst trains 525. The burst SCS waveform 524 and tonic SCSwaveform 526 may be delivered through the same electrode combinations ordelivered from different combinations of electrodes.

The hybrid therapies 502 and 522 (FIGS. 5A and 5B) each deliver twodifferent stimulation modalities. The different stimulation modalities(KHFSCS and tonic, or burst and tonic) may be delivered from differentelectrode contact pairs, or from the same electrode contact pair.

In accordance with embodiments herein, the hybrid therapies 502 and 522may be generated utilizing two stimulation sources (either current orvoltage sources), where one stimulation source generates the tonic SCSwaveform, while the other stimulation source generates the KHFSCS orburst SCS waveform. Optionally, a single stimulation source may beutilized, such as by providing an electronic switch, controlled by thecontroller 151 or a microprocessor, to apply the appropriate stimulationmodality to the selected electrodes/contacts at the designated time. Forexample, a single current or voltage source may generate the KHFSCS orburst SCS waveform.

For hybrid stimulation, the two stimulation modalities (KHFSCS, burstSCS, and/or low-frequency tonic SCS) can be delivered using monopolar orbipolar or tripolar configurations. Optionally, the two stimulationmodalities may have different stimulation amplitudes. Optionally, thehybrid therapy of KHFSCS or burst SCS, with low-frequency tonic SCS, maybe delivered from a paddle SCS lead and/or percutaneous SCS lead.

Hybrid stimulation may afford relative advantages. First, the tonic SCSmay be configured to steer current into the dermatomal zones within thedorsal column that correspond to patients' region of pain. For example,paresthesia mapping may be utilized with tonic SCS to obtain idealanalgesia coverage. Second, a neuronal activation threshold generally isless for low-frequency tonic SCS, as compared to KHFSCS. Accordingly,the tonic SCS may enable overall energy usage to be lower with hybridstimulation than with KHFSCS alone. Third, simultaneous use of tonicSCS, in combination with KHZSCS or burst SCS, facilitates blocking ofaction potential propagation in the large fibers that generateparesthesia.

Optionally, the controller 151 may utilize current steering to directthe tonic SCS pulses to dermatomes of interest.

FIG. 6 illustrates an example of a portion of a lead that may beutilized in accordance with embodiments herein. The lead includes apaddle shaped distal portion 602 that retains a plurality of electrodes604 arranged in a two-dimensional array of rows and columns. The paddleshaped distal portion 602 is oriented along the spinal column with thecranial direction extending in the direction of arrow 606. Whendelivering a hybrid therapy, in accordance with some embodiments, afirst electrode combination 608 may be designated to deliver the tonicSCS waveform, while a second electrode combination 610 may be designatedto deliver the second SCS waveform (e.g. KHFSCS or burst). In theillustrated embodiment, the second electrode combination 610 (utilizedto deliver the KHFSCS or burst SCS waveform) is positioned morecranially along the distal portion 602, relative to the position of thefirst electrode combination 608 (utilized to deliver the tonic SCSwaveform), in order to afford better blocking characteristics for actionpotentials propagating along the large diameter A. beta. fibers thatwould otherwise cause paresthesia sensations if reaching the brain.

ECAP Frequency Content Analysis

FIG. 7 illustrates a method to determine a stimulation therapy throughanalysis of evoked compound action potentials (ECAP) signals generatedin response to candidate stimulation waveforms in accordance withembodiments herein. The operations of FIG. 7 may be implemented by oneor more processors, such as within an implantable pulse generator,external programmer, another external device and the like. The IPG,external programmer or other external device are coupled to a leadhaving at least one stimulation electrode that is implanted at a targetposition proximate to nervous tissue of interest. The operations of FIG.7 may be implemented in place of, or in parallel with, the operations ofFIGS. 4A and 4B.

At 702, the method defines one or more candidate stimulation waveform tobe used. The candidate stimulation waveform is defined by one or moreparameters forming a therapy parameter set. The method delivers acandidate stimulation waveform to at least one electrode locatedproximate to nervous tissue of interest. The candidate stimulationwaveform is configured to excite at least medium and large diameter A.beta. fibers of the nervous tissue of interest. As explained herein,examples of parameters within a therapy parameter set (TPS) include, butare not limited to pulse amplitude, pulse width, inter-pulse delay,number of pulses per burst, pulse frequency, burst frequency, electrodeconfiguration, electrode polarity, etc.

At 704, the controller 151 senses an ECAP signal at one or more sensingelectrodes located proximate to the nervous tissue of interest. The ECAPsignal represents ECAP recorded activity from afferent neurons carryingboth painful stimuli, generally within the A.delta. and C fibers, andnon-painful stimuli, generally within the A.beta. fibers. Optionally, anarrow band-pass filter may be applied to the ECAP signals prior toperforming the FFT in order to filter out stimulation artifacts fromKHFSCS or burst SCS candidate waveforms. The band-pass filter allows forextracting or isolating just the ECAP signals. For example, the ECAPsignals of interest have lower frequency components (1-5 kHz) than thefrequency components of the stimulation artifact (e.g., approximately 10kHz).

At 706, the controller 151 performs frequency decomposition by analyzinga frequency content of the ECAP signal to obtain ECAP frequency dataindicative of activity by medium diameter A.beta. fibers and largediameter A.beta. fibers. For example, the decomposition/analyzingoperation may include using a Fast Fourier transform to convert the ECAPsignal to a frequency domain to generate the ECAP frequency data. TheECAP frequency data includes clusters of frequency domain componentsdistributed along a frequency spectrum, where each of the clusters isassociated with one of the medium diameter A.beta. fibers, largediameter A. beta. fibers, A.delta. fibers and C fibers. The frequencycomponents associated with medium diameter A. beta. fibers, largediameter A. beta. fibers, A.delta. fibers and C fibers are separate anddistinct from one another. Accordingly, the frequency componentsassociated with the A.delta. fibers and C fibers may be filtered outwhen not of interest.

FIG. 8 illustrates examples of frequency spectrums 800-802 that may beexhibited by ECAP signals when converted to the frequency domain inaccordance with embodiments herein. In FIG. 8, the frequency spectrums800-802 are illustrated with the horizontal axis corresponding toindividual frequencies (or frequency bin) and the vertical axiscorresponding to the amount or amplitude of the action potentialactivity (also referred to as energy content) associated with eachindividual frequency (or frequency bin). The frequency spectrums 800-802are each associated with an ECAP signal sensed over a predeterminedwindow of time. For example, the ECAP signal may be sensed for a selectwindow having a width of a few hundreds of microseconds. The frequencyspectrums 800-802 may represent the Fast Fourier transform (FFT) of anindividual window of ECAP signals, or alternatively ECAP signalscollected during multiple sensing windows. The frequency spectrums800-802 are divided into frequency ranges 812-816, each of whichcorresponds to a collection of frequencies or frequency bands that areassociated with ECAP signals from particular size or types of fibers.

For example, with respect to the frequency spectrum 800, the highfrequency range 816 is associated with ECAP signals conveyed by largediameter A.beta. fibers. The medium frequency range 814 is associatedwith ECAP signals conveyed by medium diameter A. beta. fibers. Thelow-frequency range 812 is associated with ECAP signals conveyed bymedium and small diameter A.beta. fibers. The cut off frequenciesbetween the ranges 812-816 may be manually set by an administrativeperson, a physician or otherwise. Optionally, the cutoff frequenciesbetween the ranges 812-816 may be automatically determined by the NSsystem 100 over a period of time based on patient and physicianfeedback.

The frequency spectrums 800-802 include ECAP frequency data thatcomprises a large diameter A.beta. (LDAB) component and a mediumdiameter A.beta. (MDAB) component. The LDAB and MDAB components areassociated with individual frequency bins grouped closely with oneanother in ranges 812-815 along the frequency spectrum, where theindividual frequency bins have associated different amplitudes. The FastFourier transform converts the ECAP signals to ECAP frequency data thatis separated into distinct frequency clusters 804-808, 824-828, 834-838associated with A-beta fiber components, where each of the clusters804-808, 824-828, 834-838 has a separate and distinct frequency range812-816. For example, the clusters 804 and 806 (associated with the MDABcomponent) may be located in a low frequency range 812 and a centralfrequency range 814, and the cluster 808 (associated with the LDABcomponent) is located in a high frequency range 816 (the terms low,central and high being relative to one another). The conduction velocityof action potentials is positively related to fiber diameter, withvelocities ranging between 35-75 m/s across A.beta. fiber sizes. Inpart, because of this difference in conduction velocity, the ECAPgenerated by the largest A. beta. fibers may have the shortest latencyand duration, whereas ECAPs generated by smaller fibers may have alonger latency and duration. When viewed from the frequency domain, theECAP signal components resulting from large fibers would be at thehigher end of the frequency distribution, lower for medium fibers, andat the low end for small fibers. Activation of different fiber sizescould therefore be distinguished in ECAPs recorded from either the DC orDRG by frequency components.

Each of the clusters 804-808, 824-828, 834-838 has an associated amountof frequency activity data. For example, each frequency bin within acluster has a corresponding amplitude of the action potential activityassociated with the frequency bin. The frequency activity dataassociated with an individual cluster 804-808, 824-828, 834-838 may becalculated in various manners. For example, the action potentialactivity data activity for any one of the clusters 804-808, 824-828,834-838 may correspond to an average amplitude of the frequency binstherein, or alternatively, the frequency activity data may be defined bysumming the activity levels for each of the frequency bins in thecorresponding cluster 804-808, 824-828, 834-838 (e.g., integrating theenergy within the cluster). Optionally, other mathematical factors maybe used to define the activity data associated with each fiber frequencycomponent 804-808, 824-828, and 834-838.

The frequency spectrum 800 corresponds to an ECAP signal generated inresponse to a candidate stimulation waveform having a low stimulationamplitude (e.g. approximately 0.5 V) and utilizing a KHFSCS waveform ofapproximately 6-10 kHz. The ECAP signal includes a cluster of highenergy content within the high frequency cluster 808 that represent asubstantial amount of excitation/firing of the large diameter A. beta.fiber component (e.g. greater than 11 .mu.m). The low and mediumfrequency clusters 812 and 814 are substantially void or empty of energycontent.

The frequency spectrum 801 corresponds to an ECAP signal generated inresponse to a candidate stimulation waveform having a slightly higheramplitude (as compared to the waveform utilized in connection withfrequency spectrum 800). For example, the ECAP signal delivered inconnection with frequency spectrum 801 may have resulted from acandidate stimulation waveform having an amplitude of 2-5 V and a highfrequency of 4-10 kHz. In the example of frequency spectrum 801, thecandidate stimulation waveform caused the medium diameter A. beta. fibercomponent to fire, while the large diameter A. beta. fiber component didnot fire at all or conveyed slight energy content (also referred to asconveying no or slight action potential activity). The ECAP signalincludes clusters of medium to high action potential activity within thelow and medium frequency clusters 824 and 826, thereby indicating that asubstantial amount of action potential activity within the ECAP signalis conveyed by the medium diameter A.beta. fiber component. The highfrequency cluster 828 includes very little energy content, therebyindicating that no or relatively little action potential activity withinthe ECAP signal was conveyed by the large diameter A. beta. fibercomponent.

The frequency spectrum 802 corresponds to an ECAP signal generated inresponse to a candidate stimulation waveform having an amplitude of 5 Vor greater and having a high frequency of 3-10 kHz. The candidatestimulation waveform resulted in very little or no action potentialactivity by the large diameter A.beta. fiber component and a very smallamount of action potential activity by the medium diameter A.beta. fibercomponent. The ECAP signal includes clusters 834 and 836 having lowenergy content within the low and medium frequency ranges, therebyindicating that no or relatively little excitation/firing within theECAP signal was conveyed by the medium diameter A.beta. fiber component.The frequency component 838 for the high frequency range includes noenergy content, thereby indicating that no excitation/firing within theECAP signal was conveyed by the large diameter A. beta. fiber component.

Returning to FIG. 7, at 708, the controller 151 determines the type andnature of the nerve fibers that were activated by the stimulationwaveform based on the action potential activity in each of the frequencyclusters or ranges. For example, the determining operation may analyzean action potential activity exhibited by the high, medium and lowfrequency clusters associated with each of the frequency clusters. Thedetermination may include calculating a total activity by integratingthe action potential activity at each frequency within a correspondingfrequency cluster. Optionally, a maximum, average, mean or otherstatistical indicator of action potential activity may be identified forthe action potential activity within each frequency cluster. Optionally,a morphology of the action potential activity may be determined for eachof the frequency clusters.

At 710, the controller 151 compares the nature/type of action potentialactivity (energy content) associated with each frequency component toone or more profiles. For example, the controller 151 may compare thetotal activity, morphology, maximum, average, mean, etc. to one or moretemplates or thresholds (profiles). For example, the profiles mayestablish thresholds or other criteria that indicate when certainconditions exist at the A-beta fibers. The profiles may be defined asvarious predetermined templates or thresholds that are saved inconnection with the paresthesia-abatement threshold and upper threshold.For example, one profile may correspond to the paresthesia-abatementthreshold, wherein the profile is defined as a circumstance in which thehigh frequency component has a total activity that is below a firstlarge diameter A-beta (LDAB) threshold, while the medium frequencycomponent has a total activity that is above a first medium diametera-beta (MDAB) threshold. When the total activity in the high and mediumfrequency components satisfy the first LDAB and MDAB thresholds, thecandidate stimulation waveform is recorded as the waveform associatedwith the paresthesia-abatement threshold TH_(PF).

As another example, another profile may be established for the upperthreshold, such as where the profile defines a circumstance in which thehigh frequency component has a total activity that is below the first(or a second) LDAB threshold, while the medium frequency component has atotal activity that is below a second MDAB threshold. When the totalactivity in the high and medium frequency components satisfy the secondLDAB and MDAB thresholds, the candidate stimulation waveform is recordedas the waveform associated with the upper threshold TH_(U). As oneexample, the frequency spectrum 800-802 (FIG. 8) may represent or deviceprofiles that distinguish the thresholds TH_(PF) and TH_(UP).

Flow branches from 710 based on whether a profile is met by the actionpotential activity and if so, which profile is satisfied. When theaction potential activity satisfies the profile corresponding to theparesthesia-abatement threshold, flow branches to 712. When the actionpotential activity satisfies the profile corresponding to the analgesiaupper threshold, flow branches to 714. Otherwise flow advances to 716.

At 712, the stimulation intensity associated with the candidatestimulation waveform is saved as the paresthesia-abasement threshold. At714, the stimulation intensity associated with the candidate stimulationwaveform is saved as the analgesia upper threshold. Following 712 and714, flow advances to 716. At 716, the controller 151 determines whetheradditional values for one or more parameters should be tested. If so,one or more parameters are updated at 718 and flow returns to 702. Ifnot, flow advances to 720. At 720, the stimulation therapy is set basedon the paresthesia-abatement threshold and the upper threshold asdiscussed above in connection with FIG. 4C.

Further, due to the refractory period of neurons (1-2 ms), activation ofA.beta. fibers is not expected with every stimulation pulse duringdelivery of a KHFSCS waveform. The refractory period of A-beta fibersmitigates issues associated with superposition of ECAP signals generatedfrom adjacent pulses within a KHFSCS waveform.

Optionally, the process of FIG. 7 for identifying thresholds to use forsetting stimulation therapy represents a frequency-domain ECAP approach.The frequency-domain ECAP approach may be used to replace patientresponses and to automate the programming procedure for KHFSCS or burstSCS waveforms. The process of FIG. 7 may also be used in conjunctionwith hybrid therapies that combine tonic SCS pulses withparesthesia-free KHFSCS or burst SCS waveforms to optimize analgesiacoverage in the painful body dermatomes.

Throughout the embodiments described herein, the same electrodes may beused for sensing and stimulation. Alternatively, one group of electrodesmay be used for sensing, while a different group of electrodes are usedfor stimulation. For example, the sensing electrodes may be spaced apartalong the lead from the stimulation electrodes. Optionally, the sensingelectrodes may be provided on a separate lead unique and distinct fromthe lead that includes the stimulation electrodes. For example, aconventional SCS lead may be positioned along the spinal column at adesired location in order to deliver therapy at one or more stimulationsites of interest, while a separate sensing lead is provided. As oneexample, electrodes proximate the dorsal column may be used forstimulation, while separate electrodes proximate the dorsal rootganglion (DRG) or dorsal root (DR) are used for sensing, or vice versa.As another example, stimulation and sensing may both be performed on thedorsal column. As a further option, sensing electrodes may be locatedremote from the DRG or DR, such as within the torso of the body and/oralong the extremities of the patient, such as within the arms and legs.Optionally, the burst stimulation waveform may be delivered atelectrodes proximate both of the dorsal column and the DRG, whilesensing is performed at the DRG or DR.

In various embodiments herein, conventional SCS electrodes and leads maybe used for stimulation and/or sensing, provided that the SCS electrodesare configured to be located at a desired proximity relative to a targetsite or nervous tissue of interest. Additionally or alternatively, thelead to be used for sensing may include micro electrodes (alone or incombination with conventional SCS electrodes), where the microelectrodes are configured to be placed immediately adjacent to fibers ofinterest, such as A-beta fibers, A-delta fibers, and/or C-fibers.

Optionally, the ECAP signals may be analyzed in the time domain. Forexample, the ECAP feature of interest may represent a number of positiveand negative peaks within the conduction ECAP data for a select periodof time. When processing the conduction ECAP data in the time domain,the operations may include a binning operation, in which the conductionECAP data is segmented into a series of temporal bins. Each temporal binmay include one or more occurrences of the feature of interest (e.g.spikes or peaks). The method counts a number of occurrences of thefeature of interest (FOI) within each temporal bin. For example, whenanalyzing the conduction ECAP data in the time domain, each temporal binmay correspond to ½-1 milliseconds of ECAP data. The conduction ECAPdata exhibits a number of spikes/peaks within each temporal bin, wherethe number of spikes/peaks is indicative of, and proportional to, anamount of sensory activity conveyed along the corresponding conductionnervous fibers. As more sensory activity is conveyed along theconduction nervous fibers, the number of spikes/peaks within thetemporal bins increase. Conversely, as less sensory activity is conveyedalong the conduction nervous fibers, the number of spikes/peaks withinthe temporal bins decreases.

FIG. 9 illustrates a functional block diagram of an embodiment of anelectronic control unit (ECU) 900 that is operated in accordance withthe processes described herein to analyze ECAP signals and to interfacewith one or more IPGs and/or leads with electrodes positioned atstimulation sites to deliver coupled tonic/burst therapies and/or sensesensory action potential signals. The ECU 900 may be a workstation, aportable computer, a PDA, a cell phone and the like. The ECU 900includes an internal bus that connects/interfaces with a CentralProcessing Unit (CPU) 902, ROM 904, RAM 906, a hard drive 908, thespeaker 910, a printer 912, a CD-ROM drive 914, a floppy drive 916, aparallel I/O circuit 918, a serial I/O circuit 920, the display 922, atouch screen 924, a standard keyboard connection 926, custom keys 928,and a telemetry subsystem 930. The internal bus is an address/data busthat transfers information between the various components describedherein. The hard drive 908 may store operational programs as well asdata, such as waveform templates and detection thresholds.

The CPU 902 typically includes a microprocessor, a microcontroller, orequivalent control circuitry, and may interface with an IPG and/or lead.The CPU 902 may include RAM or ROM memory, logic and timing circuitry,state machine circuitry, and I/O circuitry to interface with the IPGand/or lead. The display 922 (e.g., may be connected to the videodisplay 932). The touch screen 924 may display graphic informationrelating to the CNS 110. The display 922 displays various informationrelated to the processes described herein. The touch screen 924 acceptsa user's touch input 934 when selections are made. The keyboard 926(e.g., a typewriter keyboard 936) allows the user to enter data to thedisplayed fields, as well as interface with the telemetry subsystem 930.Furthermore, custom keys 928 turn on/off 938 (e.g., EWI) the ECU 900.The printer 912 prints copies of reports 940 for a physician to reviewor to be placed in a patient file, and speaker 910 provides an audiblewarning (e.g., sounds and tones 942) to the user. The parallel I/Ocircuit 918 interfaces with a parallel port 944. The serial I/O circuit920 interfaces with a serial port 946. The floppy drive 916 acceptsdiskettes 948. Optionally, the floppy drive 916 may include a USB portor other interface capable of communicating with a USB device such as amemory stick. The CD-ROM drive 914 accepts CD ROMs 950.

The CPU 902 is configured to analyze ECAP signals collected by one ormore electrodes. The CPU 902 includes a therapy circuit module 964 thatis configured to control delivery of candidate and therapy waveforms.The therapy circuit module 964 is further configured to control deliveryof current pulses configured as a burst SCS or KHFSCS stimulationwaveform to at least one electrode and optionally tonic SCS pulses.

The CPU 902 also includes a delay adjustment circuit module 962 thatadjusts the delays between and within the tonic and burst stimulationwaveforms. The delay adjustment circuit module 962 also adjusts thedelay between and within the KHFSCS and tonic SCS waveforms for KHFSCSplus tonic hybrid stimulation.

The CPU 902 also includes an ECAP analysis circuit module 968 thatreceives sensed ECAP signals from at least one electrode on the lead,and analyzes the ECAP signals as described herein.

The telemetry subsystem 930 includes a central processing unit (CPU) 952in electrical communication with a telemetry circuit 954, whichcommunicates with both an ECAP circuit 956 and an analog out circuit958. The circuit 956 may be connected to leads 960. The circuit 956 mayalso be connected to implantable leads to receive and process ECAPsignals. Optionally, the ECAP signals sensed by the leads are thentransmitted, to the ECU 900, wirelessly to the telemetry subsystem 930input.

The telemetry circuit 954 is connected to a telemetry wand 961. Theanalog out circuit 958 includes communication circuits to communicatewith analog outputs 963. The ECU 900 may wirelessly communicate with theCNS 110 and utilize protocols, such as Bluetooth, GSM, infrared wirelessLANs, HIPERLAN, 3G, satellite, as well as circuit and packet dataprotocols, and the like. Alternatively, a hard-wired connection may beused to connect the ECU 900 to the CNS 110.

One or more of the operations described above in connection with themethods may be performed using one or more processors. The differentdevices in the systems described herein may represent one or moreprocessors, and two or more of these devices may include at least one ofthe same processors. In one embodiment, the operations described hereinmay represent actions performed when one or more processors (e.g., ofthe devices described herein) are hardwired to perform the methods orportions of the methods described herein, and/or when the processors(e.g., of the devices described herein) operate according to one or moresoftware programs that are written by one or more persons of ordinaryskill in the art to perform the operations described in connection withthe methods.

The controller 160 may include any processor-based ormicroprocessor-based system including systems using microcontrollers,reduced instruction set computers (RISC), application specificintegrated circuits (ASICs), field-programmable gate arrays (FPGAs),logic circuits, and any other circuit or processor capable of executingthe functions described herein. Additionally or alternatively, thecontrollers 151 and the controller device 160 may represent circuitmodules that may be implemented as hardware with associated instructions(for example, software stored on a tangible and non-transitory computerreadable storage medium, such as a computer hard drive, ROM, RAM, or thelike) that perform the operations described herein. The above examplesare exemplary only, and are thus not intended to limit in any way thedefinition and/or meaning of the term “controller.” The controllers andthe controller device may execute a set of instructions that are storedin one or more storage elements, in order to process data. The storageelements may also store data or other information as desired or needed.The storage element may be in the form of an information source or aphysical memory element within the controllers and the controllerdevice. The set of instructions may include various commands thatinstruct the controllers and the controller device to perform specificoperations such as the methods and processes of the various embodimentsof the subject matter described herein. The set of instructions may bein the form of a software program. The software may be in various formssuch as system software or application software. Further, the softwaremay be in the form of a collection of separate programs or modules, aprogram module within a larger program or a portion of a program module.The software also may include modular programming in the form ofobject-oriented programming. The processing of input data by theprocessing machine may be in response to user commands, or in responseto results of previous processing, or in response to a request made byanother processing machine.

It is to be understood that the subject matter described herein is notlimited in its application to the details of construction and thearrangement of components set forth in the description herein orillustrated in the drawings hereof. The subject matter described hereinis capable of other embodiments and of being practiced or of beingcarried out in various ways. Also, it is to be understood that thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereofas well as additional items.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. In addition, many modifications may be made to adapt aparticular situation or material to the teachings of the inventionwithout departing from its scope. While the dimensions, types ofmaterials and coatings described herein are intended to define theparameters of the invention, they are by no means limiting and areexemplary embodiments. Many other embodiments will be apparent to thoseof skill in the art upon reviewing the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Moreover, in the following claims, theterms “first,” “second,” and “third,” etc. are used merely as labels,and are not intended to impose numerical requirements on their objects.Further, the limitations of the following claims are not written inmeans-plus-function format and are not intended to be interpreted basedon 35 U.S.C. .sctn.112(f), unless and until such claim limitationsexpressly use the phrase “means for” followed by a statement of functionvoid of further structure.

The invention claimed is:
 1. A computer implemented method for managingneural stimulation therapy, comprising: under control of one or moreprocessors configured with program instructions, delivering a series ofcandidate stimulation waveforms having varied stimulation intensities toat least one electrode located proximate to nervous tissue of interest,wherein the delivering changes a parameter defining the candidatestimulation waveforms to vary the stimulation intensity; identifying afirst candidate stimulation waveform from the series that induces aparesthesia-abatement effect, while continuing to induce a selectanalgesic effect; identifying a second candidate stimulation waveformfrom the series that does not induce the select analgesic effect,wherein the identifying a second candidate stimulation waveformcomprises measuring a neural response to the series of candidatestimulation waveforms where medium-size Aβ fibers are blocked; andsetting a stimulation therapy based on the first and second candidatestimulation waveforms, wherein the setting operation sets thestimulation therapy to have an intensity I based on the followingequation: I=THPF+V(THU−THPF), where k represents a constant, where THPFrepresents a first intensity level corresponding to aparesthesia-abatement threshold and THU represents a second intensitylevel corresponding to an analgesic upper threshold.
 2. The method ofclaim 1, wherein the stimulation therapy blocks the large A-beta fibershaving diameters of approximately 11.0-13.0 um and activates mediumA-beta fibers having diameters of approximately 6.0-11.0 um.
 3. Themethod of claim 1, wherein at least one of the first or second candidatestimulation waveform corresponds to a high frequency stimulationwaveform or a burst stimulation waveform for spinal cord stimulation(SCS).
 4. The method of claim 3, further comprising delivering tonic SCSpulses during the stimulation therapy in combination with the at leastone of the first or second candidate stimulation waveforms.
 5. Themethod of claim 4, further comprising utilizing current steering todirect the tonic SCS pulses to dermatomes of interest.
 6. The method ofclaim 1, wherein the stimulation therapy includes first and secondstimulation modalities, the method further comprising delivering thefirst and second stimulation modalities from different first and secondelectrode combinations.
 7. The method of claim 1, further comprising:sensing evoked compound action potential (ECAP) signals; applying anarrow band-pass filter to the ECAP signals to filter out stimulationartifacts from at least one of the first and second candidatestimulation waveforms; performing a fast Fourier transform to the ECAPsignals after the filtering operation; and the identifying operationsincluding analyzing the ECAP signals in a frequency domain.
 8. Themethod of claim 7, wherein the analyzing includes determining aparameter setting associated with the stimulation therapy that yieldsECAP signals that fit select profiles.